Spatial multi-omics profiling of 49 tumors from 19 CRC patients, mapping paired primary tumors and matched liver (macro- and micrometastases) and lung metastases using spatial transcriptomics, multi-regional whole-genome sequencing (laser-capture microdissection), and high-plex protein imaging.
Liver micrometastases (CLiMi) arose from early clonal divergences and showed a stem-like, quiescent (dormancy-associated) state; macrometastases were encapsulated by myofibroblasts while micrometastases were surrounded by immunosuppressive niches with T cell exhaustion. A CLiMi-specific 6-gene signature correlated with minimal residual disease status, disease-free survival, and chemotherapy resistance across multiple independent cohorts.
Small cohort of 19 patients limits statistical power; findings are observational and spatially descriptive, requiring prospective validation; chemotherapy resistance associations are derived from independent cohorts rather than a randomized trial.
The 6-gene micrometastasis signature may serve as a tissue-based biomarker for MRD surveillance and chemotherapy resistance prediction in CRC — watch for prospective validation studies before clinical adoption. Distinct stromal and immune niches around micro- vs. macrometastases suggest that immune checkpoint or myofibroblast-targeting strategies may need to be tailored to metastatic stage.
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